TGF, Wnt/-catenin and Hippo Pathway “Cross-talk”: Myocardial Systems Biology Murmurings as the Pathways Converge.

ABSTRACT

The heart failure (HF) diseaseasome is marked by substantial alteration in networked signaling pathways. Reductionist paradigm HF investigative approaches have focused on the regulation of a single pathway or single pathway components. In support of a more comprehensive systems biology investigative paradigm, rapidly evolving experimental evidence supports extensive regulatory cross-talk between the TGF-superfamily, Wnt/-catenin and Hippo signaling systems in homeostasis, myocardial development and a variety of non-myocardial diseases. After reviewing the basic components and integrated regulation of each of these three pathways, we review landmark studies in diverse conditions and diseases highlighting the likely critical importance of regulatory cross-talk between these three pathways in the HF.